scholarly journals The Emerging Use ofIn VivoOptical Imaging in the Study of Neurodegenerative Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Aileen P. Patterson ◽  
Stephanie A. Booth ◽  
Reuben Saba
Keyword(s):  
Neurodegenerative Diseases ◽  
Optical Imaging ◽  
Neuronal Damage ◽  
Mammalian Brain ◽  
Reporter Mice ◽  
Highly Sensitive ◽  
Charged Couple Device ◽  
Living Tissues ◽  
Lateral Sclerosis

The detection and subsequent quantification of photons emitted from living tissues, using highly sensitive charged-couple device (CCD) cameras, have enabled investigators to noninvasively examine the intricate dynamics of molecular reactions in wide assortment of experimental animals under basal and pathophysiological conditions. Nevertheless, extrapolation of thisin vivooptical imaging technology to the study of the mammalian brain and related neurodegenerative conditions is still in its infancy. In this review, we introduce the reader to the emerging use ofin vivooptical imaging in the study of neurodegenerative diseases. We highlight the current instrumentation that is available and reporter molecules (fluorescent and bioluminescent) that are commonly used. Moreover, we examine howin vivooptical imaging using transgenic reporter mice has provided new insights into Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Prion disease, and neuronal damage arising from excitotoxicity and inflammation. Furthermore, we also touch upon studies that have utilized these technologies for the development of therapeutic strategies for neurodegenerative conditions that afflict humans.

scholarly journals DNAJB6b is Downregulated in Synucleinopathies

2021 ◽  
pp. 1-13
Author(s):  
Jonas Folke ◽  
Sertan Arkan ◽  
Isak Martinsson ◽  
Susana Aznar ◽  
Gunnar Gouras ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Substantia Nigra Pars Compacta ◽  
Endogenous Protein ◽  
Highly Sensitive ◽  
Brain Material ◽  
Health And Disease ◽  
Isoform B

Background: α-synuclein (α-syn) aggregation contributes to the progression of multiple neurodegenerative diseases. We recently found that the isoform b of the co-chaperone DNAJB6 is a strong suppressor of a-syn aggregation in vivo and in vitro. However, nothing is known about the role of the endogenous isoform b of DNAJB6 (DNAJB6b) in health and disease, due to lack of specific antibodies. Objective: Here we generated a novel anti-DNAJB6b antibody to analyze the localization and expression this isoform in cells, in tissue and in clinical material. Methods: To address this we used immunocytochemistry, immunohistochemistry, as well as a novel quantitative DNAJB6 specific ELISA method. Results: The endogenous protein is mainly expressed in the cytoplasm and in neurites in vitro, where it is found more in dendrites than in axons. We further verified in vivo that DNAJB6b is expressed in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), which is a neuronal subpopulation highly sensitive to α-syn aggregation, that degenerate to a large extend in patients with Parkinson’s disease (PD) and multiple system atrophy (MSA). When we analyzed the expression levels of DNAJB6b in brain material from PD and MSA patients, we found a downregulation of DNAJB6b by use of ELISA based quantification. Interestingly, this was also true when analyzing tissue from patients with progressive supranuclear palsy, a taupathic atypical parkinsonian disorder. However, the total level of DNAJB6 was upregulated in these three diseases, which may indicate an upregulation of the other major isoform of DNAJB6, DNAJB6a. Conclusion: This study shows that DNAJB6b is downregulated in several different neurodegenerative diseases, which makes it an interesting target to further investigate in relation to amyloid protein aggregation and disease progression.

scholarly journals Optical imaging-guided cancer therapy with fluorescent nanoparticles

2009 ◽  
Vol 7 (42) ◽  
pp. 3-18 ◽  
Author(s):  
Shan Jiang ◽  
Muthu Kumara Gnanasammandhan ◽  
Yong Zhang
Keyword(s):  
Cancer Therapy ◽  
Optical Imaging ◽  
Critical Role ◽  
Therapeutic Agents ◽  
Fluorescent Nanoparticles ◽  
Highly Sensitive ◽  
Imaging Probes ◽  
Recent Developments

The diagnosis and treatment of cancer have been greatly improved with the recent developments in nanotechnology. One of the promising nanoscale tools for cancer diagnosis is fluorescent nanoparticles (NPs), such as organic dye-doped NPs, quantum dots and upconversion NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. Furthermore, the emerging development of novel multi-functional NPs, which can be conjugated with several functional molecules simultaneously including targeting moieties, therapeutic agents and imaging probes, provides new potentials for clinical therapies and diagnostics and undoubtedly will play a critical role in cancer therapy. In this article, we review the types and characteristics of fluorescent NPs, in vitro and in vivo imaging of cancer using fluorescent NPs and multi-functional NPs for imaging-guided cancer therapy.

scholarly journals Identification of Lymphatic and Hematogenous Routes of Rapidly Labeled Radioactive and Fluorescent Exosomes through Highly Sensitive Multimodal Imaging

2020 ◽  
Vol 21 (21) ◽  
pp. 7850
Author(s):  
Kyung Oh Jung ◽  
Young-Hwa Kim ◽  
Seock-Jin Chung ◽  
Chul-Hee Lee ◽  
Siyeon Rhee ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Optical Imaging ◽  
Ex Vivo ◽  
Hematogenous Metastasis ◽  
Positron Emission ◽  
Highly Sensitive ◽  
Mouse Breast Cancer ◽  
Rapid Labeling ◽  
Labeling Method

There has been considerable interest in the clinical use of exosomes as delivery vehicles for treatments as well as for promising diagnostic biomarkers, but the physiological distribution of exosomes must be further elucidated to validate their efficacy and safety. Here, we aimed to develop novel methods to monitor exosome biodistribution in vivo using positron emission tomography (PET) and optical imaging. Exosomes were isolated from cultured mouse breast cancer cells and labeled for PET and optical imaging. In mice, radiolabeled and fluorescently labeled exosomes were injected both via lymphatic and hematogenous metastatic routes. PET and fluorescence images were obtained and quantified. Radioactivity and fluorescence intensity of ex vivo organs were measured. PET signals from exosomes in the lymphatic metastatic route were observed in the draining sentinel lymph nodes. Immunohistochemistry revealed greater exosome uptake in brachial and axillary versus inguinal lymph nodes. Following administration through the hematogenous metastasis pathway, accumulation of exosomes was clearly observed in the lungs, liver, and spleen. Exosomes from tumor cells were successfully labeled with 64Cu (or 68Ga) and fluorescence and were visualized via PET and optical imaging, suggesting that this simultaneous and rapid labeling method could provide valuable information for further exosome translational research and clinical applications.

Emerging Potential of Naturally Occurring Autophagy Modulators Against Neurodegeneration

2020 ◽  
Vol 26 (7) ◽  
pp. 772-779 ◽  
Author(s):  
Md. Ataur Rahman ◽  
Md Rezanur Rahman ◽  
Toyfiquz Zaman ◽  
Md. Sahab Uddin ◽  
Rokibul Islam ◽  
...  
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
Biological Activities ◽  
Naturally Occurring ◽  
Living Organisms ◽  
Therapeutic Assistance ◽  
Lateral Sclerosis ◽  
Made In

Background: Naturally-occurring products derived from living organisms have been shown to modulate various pharmacological and biological activities. Natural products protect against various diseases, which could be used for therapeutic assistance. Autophagy, a lysosome-mediated self-digestion pathway, has been implicated in a range of pathophysiological conditions and has recently gained attention for its role in several neurodegenerative diseases. Methods: In this current review, we emphasized the recent progress made in our understanding of the molecular mechanism of autophagy in different cellular and mouse models using naturally-occurring autophagy modulators for the management of several neurodegenerative diseases. Results: Accumulating evidence has revealed that a wide variety of natural compounds such as alkaloids, polyphenols, terpenoids, xanthonoids, flavonoids, lignans, disaccharides, glycolipoproteins, and saponins are involved in the modulation of the autophagy signaling pathway. These natural products have been used to treat various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, neuroblastoma, and glioblastoma. Although a number of synthetic autophagy regulators have been recognized as encouraging neurodegenerative therapeutic candidates, natural autophagy- regulating compounds have been of further interest as potential disease therapeutics, as they cause insignificant side effects. Conclusion: Existing in vitro and in vivo data are promising and highlight that naturally-occurring autophagyregulating compounds play an important role in the prevention and treatment of neurodegenerative disorders.

Single-chain Fv Antibodies for Targeting Neurodegenerative Diseases

2018 ◽  
Vol 17 (9) ◽  
pp. 671-679 ◽  
Author(s):  
Kin Yen Chia ◽  
Khuen Yen Ng ◽  
Rhun Yian Koh ◽  
Soi Moi Chye
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
Protein Aggregates ◽  
In Vivo Model ◽  
Single Chain ◽  
Abnormal Protein ◽  
Single Chain Fv

Background & Objective: Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). These abnormal proteins aggregates damage mitochondria and induce oxidative stress, resulting in neuronal cell death. Prolonged neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal protein aggregates without eliciting any adverse effects are the main treatment strategies. To overcome this, recent studies have deployed single- chain fragment variable antibodies (scFvs) to target the pathological protein aggregates, such as amyloid-beta (Aβ) peptides, α-synuclein (α-syn) and Huntingtin (Htt). To date scFv has been effective at inhibiting abnormal protein aggregates formation in both in vitro and in vivo model system of AD, PD and HD. Conclusion: Currently active research is still ongoing to improve the scFv gene delivery technology, to further enhance brain penetration, intracellular stability, solubility and efficacy of scFv intrabody.

scholarly journals In vivo optical imaging of motor neuron autophagy in a mouse model of amyotrophic lateral sclerosis

Autophagy ◽  
2011 ◽  
Vol 7 (9) ◽  
pp. 985-992 ◽  
Author(s):  
FengFeng Tian ◽  
Nobutoshi Morimoto ◽  
WenTao Liu ◽  
Yasuyuki Ohta ◽  
Kentaro Deguchi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Optical Imaging ◽  
In Vivo Optical Imaging ◽  
Lateral Sclerosis

scholarly journals Proteomic Techniques to Examine Neuronal Translational Dynamics

2019 ◽  
Vol 20 (14) ◽  
pp. 3524 ◽  
Author(s):  
Shon A. Koren ◽  
Drew A. Gillett ◽  
Simon V. D’Alton ◽  
Matthew J. Hamm ◽  
Jose F. Abisambra
Keyword(s):  
Quantitative Analysis ◽  
Neurodegenerative Diseases ◽  
Behavioral Outcomes ◽  
Spatiotemporal Dynamics ◽  
Mammalian Brain ◽  
Short Timescale ◽  
Ribosomal Function ◽  
Recent Developments ◽  
Proteomic Techniques

Impairments in translation have been increasingly implicated in the pathogenesis and progression of multiple neurodegenerative diseases. Assessing the spatiotemporal dynamics of translation in the context of disease is a major challenge. Recent developments in proteomic analyses have enabled the resolution of nascent peptides in a short timescale on the order of minutes. In addition, a quantitative analysis of translation has progressed in vivo, showing remarkable potential for coupling these techniques with cognitive and behavioral outcomes. Here, we review these modern approaches to measure changes in translation and ribosomal function with a specific focus on current applications in the mammalian brain and in the study of neurodegenerative diseases.

scholarly journals Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Min Lee ◽  
Eun Jin Yang ◽  
Sun-Mi Choi ◽  
Seon Hwy Kim ◽  
Myung Gi Baek ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Glutamate Release ◽  
Bee Venom ◽  
Microglial Cells ◽  
Excitatory Neurotransmitter ◽  
Kinase Activation ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Bee venom (BV), which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis bothin vivoandin vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS). Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38) following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases.

scholarly journals Autonomous bioluminescent systems: prospects for use in the imaging of living organisms

2019 ◽  
pp. 62-65
Author(s):  
Z.M. Osipova ◽  
A.S. Shcheglov ◽  
I.V. Yampolsky
Keyword(s):  
Optical Imaging ◽  
New Technologies ◽  
Imaging Techniques ◽  
Eukaryotic Cells ◽  
Bioluminescent Imaging ◽  
Highly Sensitive ◽  
Living Organisms

Bioluminescent systems are increasingly being used for the development of highly sensitive optical imaging techniques in vivo. However, it is necessary to inject expensive and unstable synthetic substrates (luciferins) before each analysis for most of the systems applied. Autonomous bacterial and fungal bioluminescent systems, that recently have become available for implementation in eukaryotic cells, in our opinion, may be developed into an effective tool in new technologies of bioluminescent imaging.

scholarly journals Arf1-Ablation-Induced Neuronal Damage Promotes Neurodegeneration Through an NLRP3 Inflammasome–Meningeal γδ T cell–IFNγ-Reactive Astrocyte Pathway

2020 ◽  
Author(s):  
Guohao Wang ◽  
Weiqin Yin ◽  
Hyunhee Shin ◽  
Steven X. Hou
Keyword(s):  
Immune Response ◽  
Neurodegenerative Diseases ◽  
Nlrp3 Inflammasome ◽  
Adult Mouse ◽  
Neuronal Damage ◽  
Γδ T Cells ◽  
New Paradigm ◽  
Reactive Microglia ◽  
Γδt Cells ◽  
Lateral Sclerosis

AbstractNeurodegenerative diseases are often initiated from neuronal injury or disease and propagated through neuroinflammation and immune response. However, the mechanisms by which injured neurons induce neuroinflammation and immune response that feedback to damage neurons are largely unknown. Here, we demonstrate that Arf1 ablation in adult mouse neurons resulted in activation of a reactive microglia–A1 astrocyte–C3 pathway in the hindbrain and midbrain but not in the forebrain, which caused demyelination, axon degeneration, synapse loss, and neurodegeneration. We further find that the Arf1-ablated neurons released peroxided lipids and ATP that activated an NLRP3 inflammasome in microglia to release IL-1β, which together with elevated chemokines recruited and activated γδT cells in meninges. The activated γδ T cells then secreted IFNγ that entered into parenchyma to activate the microglia–A1 astrocyte–C3 neurotoxic pathway for destroying neurons and oligodendrocytes. Finally, we show that the Arf1-reduction-induced neuroinflammation–IFNγ–gliosis pathway exists in human neurodegenerative diseases, particularly in amyotrophic lateral sclerosis and multiple sclerosis. This study illustrates perhaps the first complete mechanism of neurodegeneration in a mouse model. Our findings introduce a new paradigm in neurodegenerative research and provide new opportunities to treat neurodegenerative disorders.

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